Salivary gland branching morphogenesis is regulated by the functional integration of neuronal signaling, but the underlying mechanisms are not fully understood in aging accelerated klotho-deficient (Kl-/-) mice. Here, we investigated whether the neuropeptides substance P (SP) and neuropeptide Y (NPY) affect the branching morphogenesis of embryonic salivary glands in aging Kl-/- mice. In the salivary glands of embryonic Kl-/- mice, morphological analysis and immunostaining revealed that epithelial bud formation, neuronal cell proliferation/differentiation, and the expression of the salivary gland functional marker ZO-1 were decreased in embryonic ductal cells. Incubation with SP/NPY at E12-E13d promoted branching morphogenesis, parasympathetic innervation, and epithelial proliferation in salivary glands of embryonic Kl-/- mice. The ERK inhibitor U0126 specifically inhibited neuronal substance-induced epithelial bud formation in the embryonic salivary gland. RNA-seq profiling analysis revealed that the expression of fibroblast growth factors/fibroblast growth factors (FGFs/FGFRs) and their receptors was significantly regulated by SP/NPY treatment in the embryonic salivary gland (E15). The FGFR inhibitor BGJ389 inhibited new branching formation induced by SP and NPY treatment and ERK1/2 expression. These results showed that aging may affect virtually the development of salivary gland by neuronal dysfunction. The neuropeptides SP/NPY induced embryonic salivary gland development through FGF/FGFR/ERK1/2-mediated signaling.

Factors driving accelerated biological age (BA), an important predictor of chronic diseases, remain poorly understood. This study focuses on the impact of diet and gut microbiome on accelerated BA. Accelerated Klemera-Doubal biological age (KDM-BA) was estimated as the difference between KDM-BA and chronological age. We assessed the cross-sectional association between accelerated KDM-BA and diet/gut microbiome in 117 adult participants from the 10,000 Families Study. 16S rRNA sequencing was used to estimate the abundances of gut bacterial genera. Multivariable linear mixed models evaluated the associations between accelerated KDM-BA and diet/gut microbiome after adjusting for family relatedness, diet, age, sex, smoking status, alcohol intake, and BMI. One standard deviation (SD) increase in processed meat was associated with a 1.91-year increase in accelerated KDM-BA (p = 0.04), while one SD increase in fiber intake was associated with a 0.70-year decrease in accelerated KDM-BA (p = 0.01). Accelerated KDM-BA was positively associated with Streptococcus and negatively associated with Subdoligranulum, unclassified Bacteroidetes, and Burkholderiales. Adjustment for gut microbiome did not change the association between dietary fiber and accelerated KDM-BA, but the association with processed meat intake became nonsignificant. These cross-sectional associations between higher meat intake, lower fiber intake, and accelerated BA need validation in longitudinal studies.

The article presents a comparative analysis of the process of population aging in the context of demographic and professional risks of depopulation among working population in Russia. The values of the main medical and demographic indicators of population aging for Russia and developed countries were given. The results of UN forecasts, probabilistic forecasts of the total number and some characteristics of the age-sex structure for the population of the Russian Federation were analyzed. The state of demographic disadvantage in Russia and in the world was convincingly shown. Particular attention was paid to the consideration of the demographic risks of a reduction in the working-age population and an increase in the burden on the working-age population. The need for further research on the use of geroprotectors and modern gerontotechnologies as means and methods for preventing premature decline in work ability, slowing down the aging process of workers, reducing the mortality rate among working population and increasing professional longevity has been proven.
В статье представлен сравнительный анализ процесса старения населения в контексте демографических и профессиональных рисков депопуляции работающего населения в России. Приведены основные медико-демографические показатели старения населения для России и развитых стран. Проанализированы результаты прогнозов ООН, вероятностных прогнозов общей численности и ряда характеристик структуры по возрасту и полу для населения РФ. Убедительно показано состояние демографического неблагополучия в России и мире. Особое внимание уделено рассмотрению демографических рисков сокращения численности населения в рабочих возрастах, увеличению нагрузки на трудоспособное население. Доказана необходимость дальнейших исследований, посвященных использованию геропротекторов и современных геронтотехнологий в качестве средств и методов профилактики преждевременного снижения профессиональной работоспособности, замедления процессов старения организма работающих, снижения уровня смертности трудоспособного населения и увеличения профессионального долголетия.

The increasing global utilization of biodegradable plastics due to stringent regulations on traditional plastics has caused a significant rise in microplastic (MPs) pollution in aquatic ecosystems from biodegradable products. However, the environmental behavior of biodegradable MPs remains inadequately elucidated. This study explored the aging processes of polylactic acid (PLA) and polystyrene (PS) under a heat-activated potassium persulfate (K2S2O8) system, as well as their adsorption characteristics towards tetracycline (TCs). In comparison to PS, the surface structure of PLA experienced more pronounced changes over aging, exhibiting evident pits, cracks, and fragmentation. The carbonyl index (CI) and oxygen/carbon ratio (O/C) of PS displayed exponential growth over time, whereas the values for PLA showed linear and exponential increases, respectively. The adsorption capacity of TCs by PS and PLA aged for 6 days increased from 0.312 mg‧g-1 and 0.457 mg‧g-1for original PS and PLA, respectively, to 0.372 mg‧g-1 and 0.649 mg‧g-1. Meanwhile, the adsorption rate (k2 values) for TCs decreased by 42.03 % for PS and 79.64 % for PLA compared to their initial values. The findings indicated that biodegradable PLA-MPs may exhibit higher tetracycline carrying capacities than PS, potentially increasing environmental and organismal risks, particularly in view of aging effects.

A model for accelerated aging in mice was developed: CB6F2 mice aged 39-45 days were exposed to fractionated 4-fold relatively uniform γ-radiation (137Cs, 0.98 Gy/min) at a total dose of 6.8 Gy. Radiation exposure led to delayed active growth, leukopenia, and lymphopenia for over 1 year during the post-radiation period. The death of irradiated males and females occurred significantly earlier than in control group animals. Median lifespans in the experimental group were 35-38% lower than in the control group (p<0.001). Ionizing radiation exposure led to the early development of hair depigmentation, cachexia, and the development of aging-associated diseases. In irradiated mice, oncological pathology constituted 30-35% in the mortality structure, which is twice as often as in the control group. The developed model can be used to study the pathogenesis of accelerated aging under radiation exposure and the search for means of its prevention and treatment.

Aging of polymers is a natural process that occurs during their usage and storage. Predicting the lifetime of polymers is a crucial aspect that should be considered at the design stage. In this paper, a series of bio-based thermoplastic poly(ether-urethane) elastomers (bio-TPUs) with modified hard segments were synthesized and investigated to understand the structural and property changes triggered by accelerated aging. The bio-TPUs were synthesized at an equimolar ratio of reagents using the prepolymer method with the use of bio-based poly(trimethylene ether) glycol, bio-based 1,3-propanediol, and hexamethylene diisocyanate or hexamethylene diisocyanate/partially bio-based diisocyanate mixtures. The polymerization reaction was catalyzed by dibutyltin dilaurate (DBTDL). The structural and property changes after accelerated aging under thermal and hydrothermal conditions were determined using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and dynamic mechanical thermal analysis (DMTA). Among other findings, it was observed that both the reference and aged bio-TPUs decomposed in two main stages and exhibited thermal stability up to approximately 300 °C. Based on the research conducted, it was found that accelerated aging impacts the supramolecular structure of TPUs.

Cystathionine γ-lyase (CSE) is a major enzyme that produces hydrogen sulfide (H2S). Herein, we report how CSE plays a previously unknown role in regulating the antioxidant effects of the mitochondria in human umbilical vein endothelial cells by releasing H2S nearby under stress conditions. We found that H2S partially promoted angiogenesis in the endothelial cells through the AKT/nuclear factor erythroid 2-related factor 2 (AKT/NRF2) signaling pathway. H2S improved mitochondrial function by altering the expressions of the mitofusin2 and dynamin-1-like mitochondrial fission proteins to inhibit oxidative stress and enhance NRF2 nuclear translocation. CSE is located only in the cytoplasm and not in the mitochondria, but it is transported to the vicinity of the mitochondria to produce H2S, which plays an antioxidant role in human umbilical vein endothelial cells under stress. The CSE mutant (with mutated CSE activity center: CSED187A) partially decreased the effects on promoting angiogenesis, resisting oxidative stress, and entering the mitochondria. These results show that CSE translocation is a unique mechanism that promotes H2S production inside the mitochondria under stress stimulation. Therefore, the CSE mutant site (CSED187A) may be a potential target for drug therapy.

BACKGROUND: Individuals with bipolar disorders (BD) have an estimated loss of life expectancy around 10-15 years. Several laboratory-measured biomarkers of accelerated aging exist (e.g., telomere length), however with a questionable transferability to bedside. There is a need for easily and inexpensively measurable markers of aging, usable in routine practice, such as BioAge.
METHODS: We calculated BioAge that estimates biological age based on routine blood tests and a physical exam, in a sample of 2220 outpatients with BD. We investigated associations between BioAge Acceleration (BioAgeAccel), which is an indicator of accelerated aging, and sociodemographic variables, clinical variables, and current psychotropic medication use.
RESULTS: Mean chronological age was 40.2 (±12.9). Mean BioAge was 39.1 (±12.4). Mean BioAgeAccel was 0.08 (±1.8). A minority of individuals (15%) had a BioAgeAccel above 2 years. Multivariable analyses suggested strong associations between a higher BioAgeAccel and younger age, male sex, overweight and sleep disturbances. Regarding current psychotropic medication use, discrepancies between univariate and multivariate analyses were observed.
CONCLUSIONS: A minority of individuals with BD had an accelerated aging as measured by BioAge. We identified associations with potentially modifiable factors, such as higher body mass index and sleep disturbances, that are however nonspecific to BD. These results require replications in independent samples of individuals with BD, and comparisons with a control group matched for age and gender. Longitudinal studies are also required to test whether any change in metabolic health, or sleep might decrease BioAgeAccel.

OBJECTIVE: Using data from the National Health Interview Survey (NHIS), this study examined the odds of functional limitations across nine domains by cancer status (with vs. without cancer history) and age group (18-44, 45-64, 65 + years).
METHODS: Participants were 151,509 adults in the 2014-2018 NHIS. Functional limitations included self-reported difficulty conducting nine activities. Data were analyzed using age-stratified multivariate logistic regression (no limitation vs. limited in any way; minor limitation vs. major limitation) and are reported as covariate-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). To gather insight on the influence of cancer, compared to aging without a history of cancer, on functional limitations, we also conducted exploratory regression analyses comparing all cancer by age groups to 18-44 year-olds without a cancer history.
RESULTS: Cancer survivors (n = 12,518) were more likely to report a limitation than adults without cancer (n = 138,991). Age-stratified ORs for 1 + limitation were 2.75 (95% CI 1.98, 3.81) among 18-44 year-olds, 2.42 (95% CI 2.00, 2.93) among 45-64 year-olds, and 1.59 (95% CI 1.39, 1.82) among 65 + year-olds. Cancer survivors were more likely to report major limitations across multiple domains, with age-stratified ORs ranging from 1.18 (65 + year-olds, stooping limitation) to 2.28 (18-44 year-old, sitting limitation). ORs from exploratory analyses were lowest among 45-64 year-old adults without a cancer history (2.69-4.42) and highest among older adult cancer survivors (3.42-14.73).
CONCLUSIONS: Cancer was associated with limitations across age groups, with the highest age-stratified ORs observed among younger adults and for mobility and lower-extremity limitations. Stronger efforts to assess limitations as part of routine care and implement targeted interventions to address limitations are needed.
CONCLUSIONS: Functional limitations have been linked with poorer aging trajectories and lower quality of life in cancer and non-cancer populations. Routine screening to identify and discuss functional limitations with cancer patients may help reduce the burden of such limitations on survivors.

BACKGROUND: Obesity correlates with accelerated aging. This study aims to investigate the association between the visceral adiposity index (VAI) and accelerated aging.
METHODS: Biological aging was evaluated by phenotypic age acceleration (PhenoAgeAccel). Utilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2010, we employed weighted multivariable logistic regression models, along with subgroup analysis, to examine the association between VAI and PhenoAgeAccel. Moreover, smooth curve fitting was utilized to identify potential nonlinear association, complemented by a two-piece linear regression model to investigate threshold effects.
RESULTS: Of the included 11,340 participants aged 20 years and older, the mean (95% CI) age was 46.569 (45.946, 47.191) years, and 49.189% were male. The mean (95% CI) VAI for all participants was 2.176 (2.114, 2.238), and the mean (95% CI) PhenoAgeAccel was -6.306 (-6.618, -5.994) years. In the fully adjusted model, each incremental unit increase of VAI was associated with a 0.312-year increase in PhenoAgeAccel (β = 0.312, 95% CI: 0.217, 0.408). This positive association was more statistically significant among individuals with cancer. Furthermore, a segmented association was observed between VAI and PhenoAgeAccel, with a turning point identified at 10.543. Below this threshold, VAI exhibited a positive correlation with PhenoAgeAccel (β = 0.617, 95% CI: 0.499, 0.735), while beyond it, the association became nonsignificant.
CONCLUSIONS: This study demonstrated a positive association between VAI and accelerated aging within a nationally representative population. The findings suggest that controlling adiposity may exert anti-aging effects and help prevent aging-related diseases.